Gilmour's Rattle That Lock topped the official chart nearly 20,000 copies ahead of Del Rey's record, Honeymoon.
It is the guitarist's second solo number one, after 2006's On An Island. He last topped the charts in November, with Pink Floyd's The Endless River.
"It's thrilling to get a number one," he said. "We all want to hit the top spot, however long we've been at it."
Gilmour easily outpaced the competition in a big week for new releases. He was joined in the Top 40 by new albums from Keith Richards, Drake & Future and Gabrielle Aplin.
Cliff Richard scored his 43rd top 10 album with the greatest hits collection 75 at 75, which landed at number four.
And country singer Ryan Adams also made a new appearance at 19, thanks to his "cover album" of Taylor Swift's 1989.
The original was two places higher, marking its 48th week in the top 40.
In the singles chart, Justin Bieber spent a third week at number one with his tropical dance track, What Do You Mean? - which was streamed 3.2 million times over the last week.
The Canadian singer has a fight on his hands next week from Sam Smith's Bond theme, Writing's On The Wall, which has already  topped the iTunes chart after eight hours on sale.
Elsewhere in the top 40, Ellie Goulding scored her tenth Top 10 hit with On My Mind - the first single from her forthcoming album Delirium.
The song was originally released last Thursday, making it chart-eligible for 24 hours, during which time it reached number 165. This week, it climbed 158 places to land at number seven.
Other new entries included Runnin' (Lose It All), a collaboration between Beyonce and British producer Naughty Boy, which debuted at 11.
One Direction's Infinity, which became available on Tuesday to coincide with the announcement of the band's fifth album, Made In The AM, made its initial chart showing at number 36.
As well as Sam Smith, this week sees new singles from Little Mix and Rudimental featuring Ed Sheeran.
New Order, Disclosure, Chvrches and former Westlife member Shane Filan will all be vying to score the number one album.
Lana Del Rey has been denied her third consecutive number one on the UK album chart by Pink Floyd star David Gilmour.