diff --git a/cpp/src/arrow/filesystem/s3fs.cc b/cpp/src/arrow/filesystem/s3fs.cc
index 04774171503..8cfc2204162 100644
--- a/cpp/src/arrow/filesystem/s3fs.cc
+++ b/cpp/src/arrow/filesystem/s3fs.cc
@@ -881,6 +881,11 @@ class S3ClientFinalizer : public std::enable_shared_from_this<S3ClientFinalizer>
 
   auto LockShared() { return std::shared_lock(mutex_); }
 
+  void Initialize() {
+    std::unique_lock lock(mutex_);
+    finalized_ = false;
+  }
+
  protected:
   friend class S3ClientHolder;
 
@@ -3419,22 +3424,20 @@ struct AwsInstance {
 
   // Returns true iff the instance was newly initialized with `options`
   Result<bool> EnsureInitialized(const S3GlobalOptions& options) {
-    // NOTE: The individual accesses are atomic but the entire sequence below is not.
-    // The application should serialize calls to InitializeS3() and FinalizeS3()
-    // (see docstrings).
-    if (is_finalized_.load()) {
-      return Status::Invalid("Attempt to initialize S3 after it has been finalized");
-    }
-    bool newly_initialized = false;
     // EnsureInitialized() can be called concurrently by FileSystemFromUri,
     // therefore we need to serialize initialization (GH-39897).
-    std::call_once(initialize_flag_, [&]() {
-      bool was_initialized = is_initialized_.exchange(true);
-      DCHECK(!was_initialized);
+    // We use a mutex instead of std::call_once to allow re-initialization after
+    // finalization (as supported by the AWS SDK).
+    std::lock_guard<std::mutex> lock(init_mutex_);
+
+    if (!is_initialized_.load()) {
+      // Not already initialized, allow re-initialization after finalization
+      is_finalized_.store(false);
+      is_initialized_.store(true);
       DoInitialize(options);
-      newly_initialized = true;
-    });
-    return newly_initialized;
+      return true;  // newly initialized
+    }
+    return false;
   }
 
   bool IsInitialized() { return !is_finalized_ && is_initialized_; }
@@ -3442,6 +3445,12 @@ struct AwsInstance {
   bool IsFinalized() { return is_finalized_; }
 
   void Finalize(bool from_destructor = false) {
+    std::unique_lock<std::mutex> lock(init_mutex_, std::defer_lock);
+    // Don't try to acquire the lock from destructor to avoid potential deadlocks
+    if (!from_destructor) {
+      lock.lock();
+    }
+
     if (is_finalized_.exchange(true)) {
       // Already finalized
       return;
@@ -3508,12 +3517,13 @@ struct AwsInstance {
     aws_options_.httpOptions.compliantRfc3986Encoding = true;
     aws_options_.httpOptions.installSigPipeHandler = options.install_sigpipe_handler;
     Aws::InitAPI(aws_options_);
+    GetClientFinalizer()->Initialize();
   }
 
   Aws::SDKOptions aws_options_;
   std::atomic<bool> is_initialized_;
   std::atomic<bool> is_finalized_;
-  std::once_flag initialize_flag_;
+  std::mutex init_mutex_;
 };
 
 AwsInstance* GetAwsInstance() {