It is the deadliest mass shooting in modern US history and the death toll is expected to rise.
Here is a list of some of the worst mass shootings in America since 1949 (the death of the shooter/s if killed or took their own life is not included in the total):
Pulse nightclub, Orlando - 49 killed
Fifty-eight people were also injured.
So-called Islamic State claimed responsibility for the attack but investigators found no clear evidence Mateen was directed by the terror group.
Virginia Tech massacre - 32 killed
On April 16, 2007, student Seung Hui Choi, killed 32 people and wounded 17 others, before killing himself on the campus of Virginia Polytechnic Institute and State University in Blacksburg, Virginia.
Sandy Hook Elementary School - 26 killed
The murder of 26 people, including 20 children, at an elementary school in Newtown, Connecticut, in December 2012, sent shock-waves across America and beyond.
Then US President Barack Obama was unable to hold back tears as he spoke about the youngest victims of the Sandy Hook shootings while speaking about measures to reduce gun violence.
Luby's Cafeteria, Texas - 23 killed
In 1991, George Hennard opened fire at a cafe in Killen, Texas, killing 23 people. He then killed himself.
McDonald's, California - 21 killed
In 1984, 21 people were killed in a McDonald's in San Ysidro, California by an out-of work security guard called James Huberty. He was later killed by police.
San Bernardino, Calfornia - 14 killed
The married couple were said to have been radicalised "for quite some time" before the deadly attack.
Columbine shooting, Colorado - 13 killed
On April 20, 1999, 18-year-old Eric Harris and Dylan Klebold opened fire at Columbine High School in Colorado, killing 12 classmates and a policeman before themselves.
Twenty-four other people were injured.
The shooting led to a renewed focus on gun violence and prompted Michael Moore's Oscar-winning documentary Bowling for Columbine.
Post office shooting, Oklahoma - 14 killed
In 1986, 14 people people were shot by Pat Sherrill inside a post office in Edmond, Oklahoma.
Fort Hood, Texas - 13 killed
Army psychiatrist Nidal Malik Hasan killed 13 people and injured 32 at military base Fort Hood, Texas, during a shooting rampage in November 2009.
Hasan carried out the shooting just days before he was to be deployed to Afghanistan and said it was in protest of what he called a US war on Islam.
He was convicted and sentenced to death.
Aurora cinema shooting - 12 killed
At least 12 people were killed and 58 injured when James Holmes carried out an attack at a cinema in Aurora, Colorado.
He released a canister of gas and then opened fire during the opening night of the Batman movie The Dark Knight Rises in 2012.
Holmes plead not guilty by reason of insanity but was convicted of murder in 2015 and sentenced to life in prison.
US shooting sprees go back decades
The trend of deadly shooting sprees in the United States stretches back decades.
In 1966, sixteen people were killed and more than 30 wounded during a 96-minute rifle rampage by student Charles Whitman at the University of Texas in Austin.
Ten years later in 1976, seven people were killed in the library of California State University, Fullerton.
In 1949, 28-year-old Howard Unruh, carried out one of America's most infamous mass shootings, killing 13 people, three of them children, in Camden, New Jersey.
The World War II veteran was diagnosed with paranoid schizophrenia and committed to a state mental institution. He died at the age of 88 in 2009.