He played college football for the Washington Huskies, and was selected by the San Francisco 49ers in the fourth round of the 2007 NFL draft.

He started playing football with the Tri-City Falcons which is a Pop Warner team in Harbor City, California.

[2] In his rookie season, he played in ten games, recording 15 tackles as a backup to then-starting safety Mark Roman.

Goldson made his NFL debut as a starter against the divisional rival Arizona Cardinals on September 13, where the 49ers were victorious on the season opener, winning 20–16 against the reigning NFC conference champions.

He had a career-high 6 interceptions and 9 pass deflections during the regular season and is now known to be one of the hardest hitting safeties in the NFL.

[3] On December 20, 2012, he was fined $77,500 for uniform violations and a helmet-to-helmet collision with Patriots tight end Aaron Hernandez.

He joined newly arrived cornerback Darrelle Revis and 43rd overall draft pick Johnthan Banks.

[5] On September 16, 2013, Goldson was suspended for one game for his helmet-to-helmet hit on New Orleans Saints running back Darren Sproles the previous day.

[11] On August 28, 2016, Goldson was signed by the Atlanta Falcons to fill a backup role due to safety Keanu Neal injuring his knee.