2000年美國職棒大聯盟球季是美國聯盟和國家聯盟共同存在後的第100個賽季。該年的世界大賽由洋基4勝1敗擊敗大都會,拿下世界大賽三連霸。這也是大聯盟截至2021年止,最後一次出現世界大賽連霸。
這年大聯盟一共出現5693支全壘打,再次刷新紀錄。同時這年也是大聯盟繼1989年來首次沒有出現無安打比賽,也沒有任何球隊拿下100勝。
以往大聯盟美聯和國聯的主審是分開進行執法的,不過大聯盟在這年進行整合,不論哪個聯盟的主審都可以跨聯盟進行執法。
- 3月29日,小熊隊在東京巨蛋進行開幕戰,這是大聯盟首次在北美地區以外進行例行賽。[31]
- 4月3日,大聯盟首次出現5人在開幕戰達成雙響砲。[32]
- 4月9日,雙城隊的Ron Coomer、Jacque Jones和Matthew LeCroy完成背靠背靠背開轟,不過皇家隊的卡洛斯·貝爾川、傑梅恩·戴伊和Mike Sweeney也在同場比賽完成此成就,為大聯盟頭一遭。[34]
- 4月30日,紅雀隊單月共敲出55轟,寫下大聯盟紀錄。[38]
- 5月11日,釀酒人隊和小熊隊進行了一場長達4小時22分鐘的比賽,寫下國聯正規9局比賽的最長時間紀錄。[40]
- 5月19日,海盜隊的捕手Jason Kendall成為隊史首位達成完全打擊的選手。[42]
- 5月29日,運動家隊的二壘手Randy Velarde策動獨力三殺,為大聯盟史上第11人。[44]
- 6月16日,在出現3次守備失誤後,洋基隊的二壘手Chuck Knoblauch主動退場,甚至在比賽進行中就離開球場。[54]
- 7月6日,紅雀隊的Keith McDonald成為史上第二位在生涯前2個打席都開轟的球員。[59]
- 7月20日,紅人隊的Mike Bell登上大聯盟,Bell家族也成為大聯盟首個祖孫3代都是大聯盟選手的家族。[60][61][62]
- 8月4日,外野手Dave Martinez加入藍鳥隊,成為大聯盟史上第9位同一年加入四支不同球隊的選手。
- 8月19日,洋基隊單局敲出3支高飛犧牲打,追平大聯盟紀錄。同天,太空人隊的傑夫·巴格威爾成為隊史首位達成生涯300轟的打者。
- 9月3日,印地安人隊的Kenny Lofton連續18場比賽在首局得分,刷新大聯盟紀錄。
- 9月4日,紅襪隊的Carl Everett成為大聯盟史上第6位在兩聯盟都打回單季100分打點的左右開弓打者。
- 9月6日,遊騎兵隊的Scott Sheldon成為大聯盟第三位於單一比賽在9個不同守位都有守備紀錄的選手。
- 9月10日,響尾蛇隊的藍迪·強森投出生涯第3000次三振。
- 9月12日,道奇隊的Dave Hansen敲出單季第七發代打全壘打,刷新大聯盟單季代打全壘打紀錄。
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