Shotwell excelled in both academics and athletics in high school, where she was on the cheerleading and varsity basketball teams while achieving at the top of her class.

Instead, Shotwell took a job in the automotive industry at Chrysler Corporation's management training program, which she initially enjoyed[11] but later grew tired of[7] and left to return to Northwestern for her graduate degree.

[14] Shotwell left Microcosm in 2002 to join SpaceX, a private, commercial, space exploration company founded by Elon Musk in the same year.

[16] In that meeting, she convinced Musk that SpaceX should hire a dedicated employee to work on business development full-time, but had not planned to join the company herself.

[17] In December 2008, Shotwell was promoted to company president following her role in the successful negotiation of the first Commercial Resupply Services contract with the NASA Associate Administrator Bill Gerstenmaier.

[13] Shotwell is the President and COO of SpaceX, responsible for day-to-day operations and managing all customer and strategic relations to support company growth.

[21] Shotwell has received particular praise from NASA Administrator Bill Nelson for her "phenomenal" leadership of SpaceX as it developed the Falcon 9 into the "workhorse" of the space launch sector.

[22] Nelson had reportedly been concerned in 2022, after Elon Musk purchased Twitter, that it would be a distraction at SpaceX, but became more comfortable after meetings with Shotwell left him feeling reassured that she was in charge of day-to-day operations.

[27][28] Following the 2022 invasion of Ukraine, Shotwell led negotiations with government agencies for requested Starlink satellite services in the country,[29] which were at first donated by SpaceX.

[35] She speaks regularly to business audiences and gave a talk for the "Captains of Industry" series at the Brent Scowcroft Center on International Security in June 2014 on private entrepreneurial accomplishments in advancing spaceflight technology.