Fellow Irish man Andrew Scott has also been nominated for his role in Black Mirror.
Olivia Colman and Jodie Comer are among the other nominees, which will take place with a largely virtual ceremony due to the pandemic.
Producers on the biggest night in US TV have sent about 130 at-home video kits to stars around the world who were unable to travel amid the health crisis.
Instead, host for the evening Jimmy Kimmel will anchor proceedings from the Staples Centre in Los Angeles, cutting to the winners for their remote acceptance speeches.
Kimmel admitted the traditional glitz and glamour could end up a “beautiful disaster” as the Emmys becomes the latest major awards show to grapple with holding a ceremony during a still-raging pandemic.
Mescal (24) received his nomination for his portrayal of Connell in the BBC Three adaption of Sally Rooney's novel, Normal People.
The series was widely praised, however it received no nomination for the limited series category, while Mescal's co-star, Daisy Edgar-Jones also missed out.
Colman is recognised in the best drama actress category for her portrayal of the Queen in Netflix’s The Crown, though faces A-list competition in the form of fellow Briton Comer, who won last year and is back again for Killing Eve.
Jennifer Aniston is nominated for her role in Apple TV+’s The Morning Show, Laura Linney is up for Ozark and Comer’s Killing Eve co-star Sandra Oh also grabbed a nod.
Other nominees include Brian Cox, Jeremy Irons, Matthew Macfadyen, Helena Bonham Carter and Thandie Newton.
Outstanding drama series, considered by many the biggest award on the night, will this year feature The Crown, Better Call Saul, The Handmaid’s Tale, Killing Eve, The Mandalorian, Ozark, Stranger Things and Succession.
HBO’s Watchmen is the most nominated show, with 26 nods, including for outstanding limited series.
The 72nd Primetime Emmy Awards take place at 1am UK time on Monday.