diff --git a/CHANGES.md b/CHANGES.md
index 8ae00afea..bb1bb8d5d 100644
--- a/CHANGES.md
+++ b/CHANGES.md
@@ -11,6 +11,7 @@
 ### Bug Fixes
 
 * Embedded newlines in quoted field values of metadata files read/written by many commands, annotation files read by `augur curate apply-record-annotations`, and index files written by `augur index` are now properly handled. [#1561][] [#1564][] (@tsibley)
+* Output written to stderr (e.g. informational messages, warnings, errors, etc.) is now always line-buffered regardless of the Python version in use.  This helps with interleaved stderr and stdout.  Previously, stderr was block-buffered on Python 3.8 and line-buffered on 3.9 and higher. [#1563][] (@tsibley)
 
 [#1561]: https://github.com/nextstrain/augur/pull/1561
 [#1562]: https://github.com/nextstrain/augur/pull/1562
diff --git a/augur/__main__.py b/augur/__main__.py
index d69eae231..59f89dd8f 100644
--- a/augur/__main__.py
+++ b/augur/__main__.py
@@ -14,11 +14,21 @@ def main():
 
         # Explicitly enable universal newlines mode so we do the right thing.
         newline=None,
+
+        # By default, stdout is line-buffered when interactive (e.g. for
+        # consistent stdio interleaving) but block-buffered when not for (I
+        # assume) better performance.
     )
     # Apply the above to stderr as well.
     sys.stderr.reconfigure(
         errors="backslashreplace",
         newline=None,
+
+        # Always line-buffer stderr since we only use it for messaging, not
+        # data output.  This is the Python default from 3.9 onwards, but we
+        # also run on 3.8 where it's not.  Be consistent regardless of Python
+        # version.
+        line_buffering=True,
     )
 
     return augur.run( argv[1:] )