diff --git a/README.md b/README.md
index f31a516..c09a0cc 100644
--- a/README.md
+++ b/README.md
@@ -27,7 +27,7 @@ We supply the extension [prepackaged](https://github.com/mlin/GenomicSQLite/rele
 Programming language support:
 
 * C/C++
-* Python ≥3.6
+* Python ≥3.10
 * Java & JVM languages
 * Rust
 
@@ -54,7 +54,7 @@ cmake --build build -j 4 --target genomicsqlite
 
 * htslib ≥ 1.9, samtools, and tabix
 * pigz
-* Python ≥ 3.6 and packages: pytest pytest-xdist pre-commit ruff
+* Python ≥ 3.10 and packages: pytest pytest-xdist pre-commit ruff
 * JDK, mvn, rust
 * clang-format & cppcheck
 
diff --git a/bindings/python/conda/genomicsqlite/meta.yaml b/bindings/python/conda/genomicsqlite/meta.yaml
index 3ae1048..6379324 100644
--- a/bindings/python/conda/genomicsqlite/meta.yaml
+++ b/bindings/python/conda/genomicsqlite/meta.yaml
@@ -20,7 +20,7 @@ requirements:
     - python
     - pip
   run:
-    - python >=3.6
+    - python >=3.10
     - sqlite >=3.31.0
 
 test:
diff --git a/bindings/python/genomicsqlite/__init__.py b/bindings/python/genomicsqlite/__init__.py
index 152a5c4..f32ffd0 100755
--- a/bindings/python/genomicsqlite/__init__.py
+++ b/bindings/python/genomicsqlite/__init__.py
@@ -8,7 +8,7 @@
 import platform
 import sqlite3
 import sys
-from typing import Any, Dict, NamedTuple, Optional  # noqa: UP035
+from typing import Any, NamedTuple
 
 _HERE = os.path.dirname(__file__)
 _YES = ("1", "true", "t", "yes", "y")
@@ -110,7 +110,7 @@ def create_genomic_range_index_sql(
     rid: str,
     beg: str,
     end: str,
-    floor: Optional[int] = None,
+    floor: int | None = None,
 ) -> str:
     return _execute1(
         conn, "SELECT create_genomic_range_index_sql(?,?,?,?,?)", (table, rid, beg, end, floor)
@@ -120,11 +120,11 @@ def create_genomic_range_index_sql(
 def genomic_range_rowids_sql(
     conn: sqlite3.Connection,
     indexed_table: str,
-    qrid: Optional[str] = None,
-    qbeg: Optional[str] = None,
-    qend: Optional[str] = None,
-    ceiling: Optional[int] = None,
-    floor: Optional[int] = None,
+    qrid: str | None = None,
+    qbeg: str | None = None,
+    qend: str | None = None,
+    ceiling: int | None = None,
+    floor: int | None = None,
 ) -> str:
     """
     Generate SQL subquery selecting the rowids of indexed_table entries overlapping a range.
@@ -145,7 +145,7 @@ def genomic_range_rowids_sql(
 
 
 def put_reference_assembly_sql(
-    conn: sqlite3.Connection, assembly: str, schema: Optional[str] = None
+    conn: sqlite3.Connection, assembly: str, schema: str | None = None
 ) -> str:
     return _execute1(conn, "SELECT put_genomic_reference_assembly_sql(?,?)", (assembly, schema))
 
@@ -154,11 +154,11 @@ def put_reference_sequence_sql(
     conn: sqlite3.Connection,
     name: str,
     length: int,
-    assembly: Optional[str] = None,
-    refget_id: Optional[str] = None,
-    meta: Optional[Dict[str, Any]] = None,
-    rid: Optional[int] = None,
-    schema: Optional[str] = None,
+    assembly: str | None = None,
+    refget_id: str | None = None,
+    meta: dict[str, Any] | None = None,
+    rid: int | None = None,
+    schema: str | None = None,
 ):
     meta_json = json.dumps(meta) if meta else None
     return _execute1(
@@ -172,14 +172,14 @@ class ReferenceSequence(NamedTuple):
     rid: int
     name: str
     length: int
-    assembly: Optional[str]
-    refget_id: Optional[str]
-    meta: Dict[str, Any]
+    assembly: str | None
+    refget_id: str | None
+    meta: dict[str, Any]
 
 
 def get_reference_sequences_by_rid(
-    con: sqlite3.Connection, assembly: Optional[str] = None, schema: Optional[str] = None
-) -> Dict[int, ReferenceSequence]:
+    con: sqlite3.Connection, assembly: str | None = None, schema: str | None = None
+) -> dict[int, ReferenceSequence]:
     table = "_gri_refseq"
     if schema:
         table = f"{schema}.{table}"
@@ -208,8 +208,8 @@ def get_reference_sequences_by_rid(
 
 
 def get_reference_sequences_by_name(
-    con: sqlite3.Connection, assembly: Optional[str] = None, schema: Optional[str] = None
-) -> Dict[str, ReferenceSequence]:
+    con: sqlite3.Connection, assembly: str | None = None, schema: str | None = None
+) -> dict[str, ReferenceSequence]:
     ans = {}
     for item in get_reference_sequences_by_rid(con, assembly, schema).values():
         assert item.name not in ans, "genomicsqlite: non-unique reference sequence names"
diff --git a/bindings/python/setup.py b/bindings/python/setup.py
index cfd8a19..88101a6 100755
--- a/bindings/python/setup.py
+++ b/bindings/python/setup.py
@@ -9,7 +9,7 @@
     README = f.read()
 
 setup(
-    python_requires=">=3.6",
+    python_requires=">=3.10",
     name="genomicsqlite",
     version=get_version(),
     url="https://github.com/mlin/GenomicSQLite",
diff --git a/ruff.toml b/ruff.toml
index 440afff..84372fb 100644
--- a/ruff.toml
+++ b/ruff.toml
@@ -2,12 +2,10 @@
 # Opt out of specific rules only where warranted; each opt-out is documented
 # inline. No rule sets are selected or opted into.
 line-length = 100 # exception to the ruff default (88): matches this codebase's black -l 100 formatting; avoids a whole-tree reformat
+target-version = "py310" # matches the package's declared floor (python_requires>=3.10); binding annotations are evaluated at runtime
 
 [lint]
-ignore = [
-    "UP006", # non-pep585-annotation: binding annotations are evaluated at runtime; package declares python_requires>=3.6
-    "UP045", # non-pep604-annotation-optional: same runtime-annotation / python>=3.6 constraint as UP006
-]
+ignore = [] # no global opt-outs; per-file opt-outs for the vendored file are scoped below
 
 [lint.per-file-ignores]
 # bindings/python/version.py is vendored (third-party, public domain) and not