Akers booted a tying 33-yarder with 3 seconds left in regulation after Sam Bradford threw a 2-yard touchdown pass to Austin Pettis with 1:09 remaining.
San Francisco linebacker Patrick Willis was flagged for holding Lance Kendricks on third down of St. Louis' final drive, a costly mistake that kept his team from getting one last chance.
On the first play of OT, Bradford completed an 80-yard pass to Danny Amendola that took St. Louis (3-5-1) to the 2, but the play was called back for an illegal formation. Some 49ers fans got up to leave, then returned to their seats.
The last tie was between Philadelphia and Cincinnati, 13-13 in 2008.
Frank Gore ran for a 20-yard touchdown with 8:23 to go in regulation just 17 seconds after backup quarterback Colin Kaepernick scurried 7 yards for a score. Kaepernick finished 11 for 17 for 117 yards and also had eight carries for 66 yards, calmly leading the Niners after it took several series to find his groove.
Gore ran for 97 yards, while Michael Crabtree made five catches for 70 yards and a 14-yard touchdown from Smith before he left the game.
Amendola returned for the Rams following a three-game absence with a shoulder injury to make 11 catches for 102 yards. Bradford went 26 for 39 for 275 yards and two touchdowns.
Smith took a hard hit on the back of the neck from linebacker Jo-Lonn Dunbar after a scramble with 1:10 left in the first quarter. But the No. 1 overall pick in the 2005 draft stayed in the game and completed his next five passes, including Crabtree's TD.
Smith, who has started 28 straight games, wound up 7 for 8 for 72 yards.
The 49ers didn't face Bradford in either meeting last season as the Rams quarterback missed six games with a high left ankle sprain. He had all kinds of extra opportunities this time.
Bradford found Steven Jackson for a 14-yard gain and first down late in the third period to keep a drive going. Jackson's helmet flew off as he bowled through Willis. The Rams benefited moments later from Dashon Goldson's 15-yard unsportsmanlike conduct penalty for taking off his helmet.
Then, defensive tackle Ray McDonald was flagged for a helmet-to-helmet hit on Bradford when he came in under the quarterback's chin, extending another Rams drive and giving them first and goal from the 7. Zuerlein kicked a 27-yard field goal.
The penalties and miscues were certainly uncharacteristic of San Francisco's defense.
Crabtree's touchdown midway through the second quarter gave him a TD reception in five straight games against the Rams. It was his third touchdown in two games, and all of his team-leading four TD catches have come in the last five games.
Kaepernick took over as Smith went to the bench to be examined by medical personnel and soon left for the locker room with a concussion.
St. Louis 14 0 3 7 0 24
San Francisco 0 7 0 17 0 24
StL • Quick 36 pass from Bradford (Zuerlein kick), 9:38.
StL • Jackson 7 run (Zuerlein kick), 1:47.
SF • Crabtree 14 pass from Ale.Smith (Akers kick), 8:13.
StL • FG Zuerlein 27, :18.
SF • Kaepernick 7 run (Akers kick), 8:40.
SF • Gore 20 run (Akers kick), 8:23.
StL • Pettis 2 pass from Bradford (Zuerlein kick), 1:09.
SF • FG Akers 33, :03.
Attendance • 69,732.
First downs 27 25
Total Net Yards 458 341
Rushes-yards 37-159 34-183
Passing 299 158
Punt Returns 3-14 2-23
Kickoff Returns 5-84 5-118
Interceptions Ret. 0-0 0-0
Comp-Att-Int 28-41-0 18-25-0
Sacked-Yards Lost 2-16 5-31
Punts 4-36.8 6-41.8
Fumbles-Lost 2-1 4-0
Penalties-yards 13-85 7-66
Time of Possession 40:45 34:15
Rushing • St. Louis, Jackson 29-101, D.Richardson 7-58, Bradford 1-0. San Francisco, Gore 21-97, Kaepernick 8-66, Hunter 3-15, Ale.Smith 2-5.
Passing • St. Louis, Bradford 26-39-0-275, Hekker 2-2-0-40. San Francisco, Kaepernick 11-17-0-117, Ale.Smith 7-8-0-72.
Receiving • St. Louis, Amendola 11-102, Kendricks 3-48, Gibson 3-47, Pettis 3-15, Jackson 2-26, St.Smith 2-11, Quick 1-36, McLeod 1-21, Pead 1-9, D.Richardson 1-0. San Francisco, Crabtree 5-70, V.Davis 4-30, Gore 3-18, K.Williams 2-24, Moss 2-19, Manningham 1-20, Hunter 1-8.
Missed Field Goals • St. Louis, Zuerlein 58 (WR). San Francisco, Akers 41 (WL).