A Kurt Thomas jumper and Tony Parker three brought the Spurs within 95-93 before Bryant received the basketball on the left wing, got into triple threat position and fired a contested trey straight through the net with 1:46 to go.
Bryant scored 23 points with six assists for the Lakers, who improved to 23-9 away from Staples Center and won their second straight to close out a three-game road trip.
Tim Duncan and Pau Gasol exchanged layups over the next two possessions, and the Lakers held on from there for the division-clinching victory.
Gasol also scored 23 points to go along with 11 rebounds, Lamar Odom added 12 points and 10 rebounds and Derek Fisher joined Trevor Ariza with 10 points apiece. The Lakers used 11 offensive rebounds to offset 11 San Antonio threes.
Michael Finley drained five of those for 25 points, joining Parker at that number. Parker also dished out nine assists, while Duncan notched a double- double with 16 points and 11 rebounds. The Spurs failed to win all four games on their homestand.
The Lakers appeared well on their way to a division title with a near perfect first quarter on both ends of the floor. Los Angeles ran off seven straight points early for an 11-4 edge -- just the tip of the iceberg in an offensive flurry. An Ariza three and Bryant jumper capped an overall 19-5 spurt for a 23-9 lead with approximately six minutes to go in the period.
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Bryant's jumper with about 10 ticks left capped the first-period scoring and opened up a 35-17 margin.
Finley's trey late in the second stanza cut the deficit to 39-31, as the Lakers mustered just four points in the first five-plus minutes. However, Los Angeles answered with eight quick points to re-gain control at 47-31 after Odom's layup.
Gasol's jumper in the closing seconds capped the scoring for a 53-38 lead after 24 minutes of action.
San Antonio did draw closer than an effective third quarter, cutting the deficit into single digits by period's end. The edge went as high as 15 points at 64-49 on two Bryant free throws, but an 11-3 spurt by the Spurs drew the home team within seven. Parker's two free throws just prior the horn made the score 78-70 entering the fourth stanza.