diff --git a/core/metacling/src/TCling.cxx b/core/metacling/src/TCling.cxx
index 904b85242bc9d..998e29cec2d64 100644
--- a/core/metacling/src/TCling.cxx
+++ b/core/metacling/src/TCling.cxx
@@ -3191,6 +3191,30 @@ void TCling::ClearStack()
    // No-op for cling due to cling::Value.
 }
 
+namespace {
+   // Re-enable JIT symbol library autoloading (independently of class/dictionary
+   // autoloading) for the lifetime of the object. See its use in TCling::Declare
+   // and #16601.
+   class EnableAutoLoadingForJITSymbolsRAII {
+      TClingCallbacks *fCallbacks;
+      bool fOldValue = false;
+
+   public:
+      EnableAutoLoadingForJITSymbolsRAII(TClingCallbacks *callbacks) : fCallbacks(callbacks)
+      {
+         if (fCallbacks) {
+            fOldValue = fCallbacks->IsAutoLoadingForJITSymbols();
+            fCallbacks->SetAutoLoadingForJITSymbols(true);
+         }
+      }
+      ~EnableAutoLoadingForJITSymbolsRAII()
+      {
+         if (fCallbacks)
+            fCallbacks->SetAutoLoadingForJITSymbols(fOldValue);
+      }
+   };
+}
+
 ////////////////////////////////////////////////////////////////////////////////
 /// Declare code to the interpreter, without any of the interpreter actions
 /// that could trigger a re-interpretation of the code. I.e. make cling
@@ -3206,6 +3230,12 @@ bool TCling::Declare(const char* code)
    SuspendAutoLoadingRAII autoLoadOff(this);
    SuspendAutoParsing autoParseRaii(this);
 
+   // The suspensions above make parsing behave like a plain compiler, but they also
+   // gate the JIT's library autoloading - and a declared global's static initializer
+   // may still need symbols from a not-yet-loaded library (e.g. TVectorT<float> from
+   // libMatrix). Re-allow autoloading for such genuine JIT symbol resolution. #16601
+   EnableAutoLoadingForJITSymbolsRAII autoLoadJITOn(fClingCallbacks);
+
    bool oldDynLookup = fInterpreter->isDynamicLookupEnabled();
    fInterpreter->enableDynamicLookup(false);
    bool oldRawInput = fInterpreter->isRawInputEnabled();
diff --git a/core/metacling/src/TClingCallbacks.cxx b/core/metacling/src/TClingCallbacks.cxx
index 771f19fe9feb3..0b4ae9c873aa1 100644
--- a/core/metacling/src/TClingCallbacks.cxx
+++ b/core/metacling/src/TClingCallbacks.cxx
@@ -97,7 +97,14 @@ class AutoloadLibraryGenerator : public llvm::orc::DefinitionGenerator {
                              llvm::orc::JITDylibLookupFlags JDLookupFlags,
                              const llvm::orc::SymbolLookupSet &Symbols) override
    {
-      if (!fCallbacks.IsAutoLoadingEnabled())
+      // The IsAutoLoadingEnabled() gate keeps speculative lookups (e.g. querying
+      // the address of a global that is not loaded) from triggering a costly scan
+      // of all libraries. But that gate is also flipped off by the class-autoloading
+      // suspension in TCling::Declare, which merely wants parsing to behave like a
+      // plain compiler - it must not stop us from autoloading a library whose
+      // symbols the emitted static-initializer code genuinely needs to run. Declare
+      // signals that case via IsAutoLoadingForJITSymbols(). See #16601.
+      if (!fCallbacks.IsAutoLoadingEnabled() && !fCallbacks.IsAutoLoadingForJITSymbols())
          return llvm::Error::success();
 
       // If we get here, the symbols have not been found in the current process,
diff --git a/core/metacling/src/TClingCallbacks.h b/core/metacling/src/TClingCallbacks.h
index f729b266ae4d4..5a81d817cfa76 100644
--- a/core/metacling/src/TClingCallbacks.h
+++ b/core/metacling/src/TClingCallbacks.h
@@ -46,6 +46,7 @@ class TClingCallbacks : public cling::InterpreterCallbacks {
    bool fIsAutoLoading = false;
    bool fIsAutoLoadingRecursively = false;
    bool fIsAutoParsingSuspended = false;
+   bool fIsAutoLoadingForJITSymbols = false;
    bool fIsCodeGening = false;
    bool fIsLoadingModule = false;
    llvm::DenseMap<llvm::StringRef, clang::DeclarationName> m_LoadedModuleFiles;
@@ -63,6 +64,12 @@ class TClingCallbacks : public cling::InterpreterCallbacks {
    void SetAutoParsingSuspended(bool val = true) { fIsAutoParsingSuspended = val; }
    bool IsAutoParsingSuspended() { return fIsAutoParsingSuspended; }
 
+   // Whether the JIT is allowed to autoload a library to resolve a symbol it
+   // genuinely needs to link and run emitted code, even while class/dictionary
+   // autoloading is suspended (as TCling::Declare does while parsing). See #16601.
+   void SetAutoLoadingForJITSymbols(bool val = true) { fIsAutoLoadingForJITSymbols = val; }
+   bool IsAutoLoadingForJITSymbols() const { return fIsAutoLoadingForJITSymbols; }
+
    bool LibraryLoadingFailed(const std::string &, const std::string &, bool, bool) override;
 
    void InclusionDirective(clang::SourceLocation /*HashLoc*/, const clang::Token & /*IncludeTok*/,
diff --git a/core/metacling/test/TClingTests.cxx b/core/metacling/test/TClingTests.cxx
index 0777ab12d6093..2a54d12864dd3 100644
--- a/core/metacling/test/TClingTests.cxx
+++ b/core/metacling/test/TClingTests.cxx
@@ -436,6 +436,21 @@ TEST_F(TClingTests, UndeclaredIdentifierCrash)
    gInterpreter->ProcessLine("for(i=0; i < 0;); // the second usage of `i` was enough to get a segfault");
 }
 
+// https://github.com/root-project/root/issues/16601
+// Declaring a global whose static initializer needs symbols from a library that
+// is not loaded yet (here libMatrix, via TVectorT) must still autoload that
+// library: TInterpreter::Declare suspends *class* autoloading while parsing, but
+// this must not prevent the JIT from materializing symbols that the emitted
+// static-initializer code genuinely requires to run.
+TEST_F(TClingTests, DeclareAutoloadsSymbolsForStaticInit)
+{
+   ASSERT_FALSE(gInterpreter->IsLoaded("libMatrix"));
+   EXPECT_TRUE(gInterpreter->Declare("#include <TVectorT.h>\n"
+                                     "const auto gROOT16601vec = TVectorT<float>(3);"));
+   // The variable must exist and be usable, i.e. its constructor ran.
+   EXPECT_EQ(3L, gInterpreter->ProcessLine("gROOT16601vec.GetNrows();"));
+}
+
 // https://github.com/root-project/root/issues/15818
 #if !defined(_MSC_VER) || defined(R__ENABLE_BROKEN_WIN_TESTS)
 TEST_F(TClingTests, VeryLongExpression)