Lowe received his first major showcase as the star of the engaging teen sitcom "Spencer" (NBC, 1984-85) playing an eccentric, discontented and lusty 16-year-old high school student. Supported by veteran character players and lively if unambitious scripts, the young actor made a memorable impression. He departed the series after a mere six episodes either due to a salary dispute or creative differences (depending upon the source). Lowe subsequently focused on improving his craft with an acting coach and stage work. He returned to TV to play the estranged son of Elizabeth Taylor's emotionally fragile faded actress on the comeback trail in the TV-movie version of "There Must Be a Pony" (ABC, 1986). Lowe later co-starred with Tommy Lee Jones and Robert Urich in "April Morning" (CBS, 1988), a period coming-of-age drama set on the eve of the American Revolution, on the "Hallmark Hall of Fame". He next starred in "No Means No" (CBS, 1988), an award-winning presentation of "CBS Schoolbreak Specials", about date rape in which Bonnie Bedelia played his mother.

Lowe gained a devoted following and considerable acclaim and notoriety as a series regular on the third and fourth seasons of the landmark family drama "Life Goes On" (ABC, 1991-93). As Jesse McKenna, the HIV-positive artist boyfriend of Becca (Kellie Martin), he movingly portrayed the different stages of a high schooler simultaneously dealing with young love and a terminal illness. Lowe won a richly deserved 1992/93 Emmy for his portrayal. The socially conscious actor also became a fixture on AIDS-related TV specials and PSAs. He went on to appear in various TV-movies and miniseries as well as several theater production. Lowe also remained devoted to acting training.

As of the mid-90s, Lowe's film career was undistinguished even as he received good notices in some obscure and quirky low-budget genre features which quickly landed on video shelves. The Norway-lensed "Apprentice to Murder" (1988) paired him with a mystical Donald Sutherland in a brooding period suspenser set in 1928 Pennsylvania. In a lighter vein, "Nobody's Perfect" (1989), a disarming Swiss co-production, found him in drag trying to get close to the college co-ed of his dreams. "Highway to Hell" (1992) found him attempting to rescue his bride (Kristy Swanson) from the forces of darkness and "Siringo" (1995) put him in Western duds as a young deputy. With four indie features in the can for 1997 release, Lowe appeared poised to make a more serious stab at a feature acting career.

Lowe ended 1996 and began the new year with an eight episode story arc on the enduringly silly sleazefest "Melrose Place" (Fox), as an eccentric computer genius with eyes for Laura Leighton's Sydney.