The Daxamite Invasion was the hostile attack in National City, Earth-38 by the alien race known as the Daxamites who had the goal of conquering the planet Earth and making it the new home for the Daxamites as well as sating Rhea's vengeance against Supergirl for turning her son against her.
However, the invasion was prevented by Lena Luthor, who spread lead into the Earth's atmosphere, causing the Daxamites to retreat.
The Prince of Daxam, Mon-El, crashed on Earth after escaping Daxam during Krypton's destruction. He was found by Kara Danvers and J'onn J'onzz. With no way of returning to Daxam, as it was reduced to a wasteland by Krypton's destruction, Mon-El was forced to remain on Earth. During this time, he eventually befriended Kara and her friends, and eventually fell in love with the Kryptonian hero. However, he kept his identity as a prince of Daxam from Kara, fearing she would reject him as her opinion of him was appalling.
Meanwhile, King Lar Gand and Queen Rhea of Daxam, escaped the planet and kept searching for their son, eventually learning from Maaldorians that he is on Earth. As they arrived, they demanded that Earth surrender Mon-El or they will invade. Unwilling to let Earth suffer because of him, he gave himself up, and Kara learned of his identity as the prince, and angrily broke up with him. However, Mon-El refused to leave Kara and declared his intent to remain to his parents. Mon-El and Kara eventually made up.
Taking on the belief that Supergirl had poisoned his sons mind, Rhea secretly placed a bounty on her. When the D.E.O. learned this, Kara and Mon-El tried to convince Rhea, but instead Rhea struck Kara with Kryptonite Sais and Mon-El left with her. Desperate to have him back, Kara begged J'onn and Alex to help her get him back. They assaulted Rhea's ship and during a fight inside, Lar Gand broke it up, and agreed to let his son go to Earth, as he had made his choice. Daxamites left Earth, but Rhea killed her husband and desired revenge against Earth and Supergirl for turning her son against her.
Rhea approached Kara's best friend, Lena Luthor, and offered her a partnership in constructing a massive transmat-portal. Learning that Rhea is an alien, Lena was first suspicious, but Rhea convinced her otherwise, unaware of Rhea's true intent. As they completed the portal, Rhea activated it, allowing the massive Daxamite fleet to enter Earth through the portal, despite the efforts of Kara, Mon-El and J'onn. To force Mon-El back into the fold, Rhea took him and Lena to her ship, with the intention to forcefully marry the two.
With the Daxamites laying siege upon National City, Kara, Alex and the D.E.O. prepared Al's Dive Bar as an underground base. Cat Grant returned to the city, and Lena's adoptive mother, Lillian Luthor, intended to save Lena, recruiting Supergirl to her aid. As Cat Grant made a broadcast to the city to stand up and fight, it distracted Rhea long enough to allow Kara, Lillian and Hank Henshaw to infiltrate her ship and rescue Lena and Mon-El. They crashed the forced wedding, and Lillian and Hank escaped with Lena. Kara let Mon-El escape, but she remained behind to confront Rhea. Meanwhile, President Olivia Marsdin ordered the D.E.O. to use a positron cannon on the Daxamite mothership, but it was destroyed by Superman. Earlier, he attempted to confront Rhea himself, but she infected him with Silver Kryptonite, causing him to hallucinate. As a result, when Kara confronted Rhea, she set Superman on her, and the two cousins fought, until Kara managed to beat him, but exhausting herself.
With Alex's assistance, Kara and Clark recuperated inside the Fortress of Solitude, and discovered the rite of Dakkam Ur, a trial by combat, which Kara intended to use to stop the invasion, despite Mon-El's protest. Kara challenged Rhea, demanding that if she wins, Rhea and the Daxamites leave Earth. Meanwhile Lena and Lillian came up with a backup plan: if Supergirl can't defeat Rhea, they will line Earth's atmosphere with lead, using a bomb developed by Lex Luthor, as Daxamites had intense allergy for it. It would also mean that if used, Mon-El will have to leave Earth. During the trial, Rhea broke the rules by ordering the fleet to attack the city, forcing Mon-El, Clark, J'onn, Alex and others to fight the Daxamites in the streets. They were joined by M'gann M'orzz and her group of reformed White Martians. Rhea also had coated her body with Kryptonite to allow herself an unfair advantage over Kara, but Kara manged to gain an upper hand. Intending to break Kara completely, Rhea ordered her fleet to destroy the city. This forced Kara to detonate the lead-bomb: the invasion was stopped, as the lead-lined atmosphere forced Daxamites to retreat. Some soldiers couldn't escape in time, and Rhea was also left behind. She begged Mon-El to save her, but he refused, as he realized that Rhea killed his father. Kara was forced to let Mon-El go, as the atmosphere would kill him, too. She tearfully confessed she loves him, before he boarded his pod and left.
Supergirl was hailed a hero after the invasion, but the loss of Mon-El caused Kara to delve more deeply into her Supergirl persona, causing her to become distant towards her friends. Six months later, she finally realized how holding on to things she has lost caused her to lose sight of the things she still has, and she slowly started to get better. The main reason for her personality change was the fear that she sent Mon-El to his death. Seven months after the invasion, Kara discovered that Mon-El was alive. He ended up into the 31st century, and returned to the past to defeat the Worldkiller Pestilence, alongside the Legion of Superheroes. Kara, J'onn and Winn discovered him inside the Legion's ship.
Morgan Edge attempted to use the lead-bomb as a cover in order to discredit Lena by blaming the lead-bomb as the reason for sudden lead-poisonings of children. But thanks to Kara and Samantha Arias, the real reason for the poisonings was discovered.