Guarantano grew up Lodi, New Jersey, and attended Bergen Catholic where he played football.

[6] He was a four-star recruit coming out of high school and top 4 dual-threat quarterback in the nation.

He threw his first collegiate touchdown to Jeff George in Tennessee's 42–7 victory over Indiana State in the second game.

[14][15] Tennessee's performance in the 2017 season resulted in the firing of head coach Butch Jones.

[16] He finished his second year with 997 passing yards and four touchdowns with a completion percentage of 62.0 when starting in six games and appeared in nine contests.

[21] Tennessee had two shots at bowl eligibility late in the 2018 season but dropped both games against Missouri and Vanderbilt to finish 5–7.

[22] As a sophomore he started all 12 games and passed for 1,907 yards and 12 touchdowns with three interceptions (the lowest since Condredge Holloway in 1972).

[32] He threw a late touchdown to Tyler Byrd to give the Volunteers a 10-point lead in the fourth quarter to help clinch the 20–10 victory.

[38] Following a victory over Vanderbilt, Tennessee finished with a 7–5 record and earned an appearance in the Gator Bowl against Indiana.

[43] Guarantano helped lead Tennessee to a 2–0 start before a 44–21 loss to #3 Georgia Bulldogs sent the season spiraling.

[48][49][50] Guarantano threw for 1,112 yards and six touchdowns with four interceptions in seven games during the 2020 season that was cut short due to the COVID-19 pandemic.

[56] After going undrafted in the 2022 NFL draft, he signed after a rookie minicamp as an UDFA-contract with the Arizona Cardinals.

[67] On January 30, 2025, Guarantano signed with the San Antonio Brahmas of the United Football League (UFL).