The area is an important thoroughfare used by trucks, public transit, cyclists and pedestrians, which connects the city to the area south of the Fraser.
Work on the off-ramps for the Knight Street Bridge will take place overnight between 8 p.m. and 5 a.m. PT to accommodate the heavy traffic in the area.
Construction on SE Marine Drive will be completed during the day, except for peak commuting times in the morning and late afternoon.
Lon LaClaire, the city's director of transportation, says there are more than 300 collisions at the intersection each year.
To reduce the number of accidents, the $5.2 million in upgrades will include an additional lane on the off-ramp and a traffic signal.
"We're expecting some pretty significant reduction in traffic collisions," LaClaire said.
City council approved the upgrades in fall 2015. The work is expected to be completed by November.
With files from Margaret Gallagher